This project represents continuing research into the relationships between psychotogenic procedures (stress, psychotomimetic drugs, etc.) and the brain amines. We are investigating the pharmacology and neurochemistry of indoleamine (especially LSD) and phenylethylamine hallucinogens and their effects on the metabolism and disposition (binding, storage, release) of the brain amines (serotonin, norepinephrine, dopamine). Our experiments are designed to elucidate the mechanisms responsible for the differences among the indoleamine hallucinogens and between the indoleamines and phenylethylamines, for the observed amine-dependent hypersensitivity to LSD, and for tolerance. Our strategy involves time-course measurements of drug and amine metabolism and disposition. Drug pretreatments and midbrain and hypothalamic lesions are utilzed to probe experimentally the amine-behavior interrelationship. Thus, this project involves a sequence of studies to specify neurochemical events relevant to behavioral changes. The current stage of the research is centered on investigation of the regional, cellular and subcellular localization in the brain of these hallucinogenic drugs, of the amines, and of drug-induced shifts in subcellular compartments, and involves the utilization of radioactive racers of high specific activity and the techniques of density gradient centrifugation, ion-exchange, get permeation and thin layer chromatography, autoraiograph of freeze-dried, dry-mounted frozen tissue sections, fluorescence histochemistry, and fluorometric analyses.